Sensitive cat syndrome (Proceedings)

Introduction & Epidemiology

Keeping cats indoors has become common veterinary advice to reduce the risk of exposure to infectious diseases and injury from vehicles or other animals. This advice may not be completely beneficial for cats, however. As early as 1925, Kirk suggested that "too close confinement to the house" increased the risk of lower urinary tract signs (LUTS). Results of subsequent epidemiological studies have confirmed his observations. Available epidemiological studies of LUTS suggest an overall incidence rate of somewhat less than 1%, and a prevalence rate from 1 to 6%; a recent study reported a rate of approximately 1.5%. Many factors associated with LUTS have been investigated. Excessive body weight and decreased activity were associated with increased risk in some studies, and cats that only had access to indoor litter pans had an increased risk of LUTS compared to cats that could eliminate outdoors. Living with other cats also has been associated with LUTS, suggesting that social interactions or a horizontally transmitted infectious agent might play a role in the development of these signs. The lack of difference between cases and controls in viral disease rates, and the increase in risk associated with the amount of time spent indoors seems to argue against an infectious agent as a common cause. Subsequent studies have found indoor housing to be associated with a variety of common disease problems of cats, including dental disease, obesity, type 2 diabetes mellitus, and hyperthyroidism. In addition to the factors listed above, a case-control study of LUTS conducted in New Zealand during 1991-1993 also reported an increased incidence of LUTS after moving to a new house within the previous three months, and during winter months; further analysis revealed a highly significant association with rainy days during the previous month rather than with season. Access to outdoor prey was found to be protective.

Dental disease is reported to be the most common current disease problem of pet cats. The two most common problems are periodontal disease and odontoclastic resorptive lesions (ORL). In 1992, Van Wessum et al. reported that ORL were present in 62% of Dutch cats and 67% of US cats examined. Two cross-sectional studies have evaluated potential risk factors for ORL in feline teeth. In the first, cats with ORL were more likely to be older, female, taking medications, and drinking city vs. well water, and less likely to play with toys, have owners who cleaned their teeth or to be fed diets with higher magnesium, calcium, phosphorus, and potassium contents. Without food intake information, the significance of the differing mineral content of the diets is unclear, although it may suggest that diets designed to influence recurrence of LUTS were fed. Indoor housing was not identified as a significant risk factor in this study. In a subsequent study, an odds ratio (OR) of 4.5 was associated with a history of dental disease (gingivitis, calculus, or periodontal disease), and ORs of 4.4 and 4.5 were found for city residence and indoor housing, respectively. Consumption of commercial treats appeared protective (OR=0.3).

Obesity in cats also is a common problem. In a study of the body condition score of more than 2000 cats presented to veterinary hospitals in the Northeastern United States in the early 1990s, veterinarians reported that 25% of cats were overweight, and owners estimated that 29% of their pets were overweight. Apartment dwelling, inactivity, middle age, being male, neutered, of mixed breeding, and certain dietary factors were associated with being overweight. The OR for indoor housing ranged from 1.6 to 15.8, depending on the parameter measured. Another study of obesity in cats living in metropolitan Perth, Western Australia, in which cats were categorized as underweight, correct-weight or overweight by their owners found an OR of 1.4 for indoor housing and 1.8 for living in houses with only one or two other cats. The ORs for neutered and crossbred cats were 2.8 and 2.1, respectively. In a recently reported study of obesity in an urban cat population in New Zealand, inactivity was identified as significant following univariate analysis, but not in the combined logistic-regression analysis. Scarlett, et al., suggested that the increased risk of obesity in apartment-dwelling cats might have been due to inactivity and boredom. Additionally, Carlstead, et al., reported that passivity and reduced activity can occur in environments containing threats perceived to be inescapable or uncontrollable.

Prior to 1979, hyperthyroidism in cats was a rare condition. A 1988 study identified an OR for indoor housing of 4 to 11.2; Siamese cats were found to be protected. In a subsequent study, a reduced risk also was identified in Siamese and Himalayan cats, and a 2- to 3-fold increase in risk was observed in cats eating a diet composed mostly of canned cat food and in those using cat litter. More recently, cats that consumed fish or liver and giblets flavors of canned cat food were at increased risk (OR=2.4).

Most of these studies, conducted over a period of more than a quarter century, have identified indoor housing as a risk factor for disease in cats. Differences among the studies, particularly those that did not find increased risk, might have occurred for a variety of reasons. The first, of course, is that indoor risk really is not a risk factor. The fact that it has been identified in different diseases studied at different times and different places, however, seems to argue against this interpretation. Differences in sample size and the questions asked undoubtedly also contributed to the differences. Additionally, the studies that did not identify associations with indoor restriction were the most recently conducted. If the majority of cats in both case and control groups (which in many studies were cats with other diseases) were housed indoor, it would be difficult to isolate this as a risk factor.

The identification of differences in breed susceptibilities also suggests that internal as well as external factors influence risk. Internal factors include temperament, genetic and experiential variables. As in other species, individual differences in temperament have been reported in cats. Also, strain differences in stress susceptibility, and individual variation in experience influence responses to the environment.

Physiology

The sensitivity of cats to their surroundings and their responses to threatening stimuli have been studied for decades; indeed, the eminent physiologist Walter B. Cannon's description of the "fight or flight" response resulted from studies of cats conducted during the first 2 decades of the 20th century. Cats are a relatively solitary species, often choosing population densities of less than 50 per square kilometer. Although free ranging male and female cats occupy overlapping home ranges of approximately 100 meters in diameter, they avoid meeting each other by keeping to a sort of time schedule. In a study of households with two cats, some 50% of time was spent out of one another's sight, even though they were most often within 1-3 meters of each other. Cats thus may be unusually susceptible to indoor restriction because of the differences between their solitary behavioral strategies and those of the pack species, including most other domestic animals, and humans.

Environments may range from benign through challenging to threatening. Animals also vary in their sensitivity to environmental stimuli, and variations in responses occur both among species and within individuals. The range of variation is large. Despite application of an identical stressor, Dumas et al., found as much as a 12-fold range in stress response among different strains of rats. Thus, in any given environment, the response of any particular animal cannot be predicted. Moreover, the environment constantly changes, and animals and environments act on each other. The environment also may elicit an uncontrolled or inappropriate stress response by reducing the animals' perception of control of the environment, or by increasing their perception of threat. Animals have been selected by evolution for reproductive success. Essential criteria for reproductive success include the ability to find mates, and to perceive and respond to environmental threats to sustain life long enough to ensure transmission of genetic material. To find mates, animals must act in the environment. Action results in acquisition of new information from the environment, collected by all the appropriate sensory apparatus of the animal (pheromonal, olfactory, gustatory, auditory, cutaneous and visual). These signals are integrated by the central nervous system (CNS), and perceived by the animal as not threatening or threatening in a constant reiterative cycle with a time constant of milliseconds.

If the animal perceives no threat, the initial course of action may progress; if a threat is perceived, however, different actions result. The threat often is called a stressor, and the actions occurring in the animal are referred to as the stress response. These responses have been selected over millennia, and so are complex and interactive, with multiple fail-safe back up systems involving immune, neurological, and vascular alterations that underlie the behavioral response. They may have developed initially as local defense responses to noxious environmental stimuli, and have been built on and expanded as the vascular and nervous systems developed increasing complexity.

Based on the evidence described above, I believe that some cats with "feline idiopathic cystitis" (FIC) may have a "Pandora syndrome" (named for the Pandora myth, which reflects my experience in studying this problem, and my optimism that hope for effective treatment remains), with multiple, complex abnormalities of the nervous and endocrine systems that likely affect more than just the bladder. Enhanced central sympathetic (noradrenergic) drive in the face of inadequate adrenocortical restraint seems to be related to maintaining the chronic disease process. These systems seem to be driven by tonically increased stress response system activity, which may represent the outcome of a developmental accident. Because of these abnormalities, treatment strategies that decrease central noradrenergic drive may be important in reducing signs of FIC; those that do not address this aspect of the disease seem to be less effective. Until more effective treatments to normalize the responsiveness of the stress response system are available, efforts to reduce input to this system by environmental enrichment seem reasonable.

Diagnosis

One also must recognize that an important limitation of many experimental studies of disease is that their focus often is limited to the organ of interest. For example, although we have identified a number of abnormalities related to the urinary bladder, we know far less about whether these are specific to the bladder, or occur in other organs as well. Based on my experiences, criteria for diagnosis of a cat with a chronic multisymptom illness, as opposed to a peripheral organ-based problem, that may benefit from inclusion of environmental enrichment include:

1. A history of early adverse experience (orphaned, bottle fed, rescued);

2. Evidence of problems in other organs (particularly preceding the presenting LUTS in the case of FIC), including behavioral, endocrine gastrointestinal, respiratory, dermatological, etc.; and

3. Evidence of familial involvement. That is, parents and or littermates have a similar illness profile

This information often has not been obtained from owners, and may be unavailable. It also is not pathognomonic for anything, only raising one's "index of suspicion" that something more systemic that would be identified by the casual observer may be going on. By taking the time to obtain a careful review of the cat's life history and conduct a thorough physical examination before assuming that the cat has a bladder or other particular disease, I have found that some cats appear to have a disease affecting the organ attributed to the presenting signs, which helpfully informs my therapeutic recommendations. I urge others not to believe me (and my biases), but to test this hypothesis for themselves. The forms we use for investigation of these cases are included as an appendix.

Treatment

1. Environmental Enrichment - Environmental enrichment is primary therapy for prevention of recurrence of FIC. This opinion is based on the documented neuroendocrine abnormalities suffered by cats with FIC, and on our clinical experience. We define environmental enrichment for indoor-housed cats to mean provision of all "necessary" resources, refinement of interactions with owners, a tolerable intensity of conflict, and thoughtful institution of change(s). Although we are not aware that a particular resource list has been validated for indoor housed cats, some recommendations are available in the many excellent publications about cat housing and behavior that currently are available. We also recommend extending the "1+1" rule traditionally applied to litter boxes (1 for each cat in the home, plus 1 more) to all pertinent resources (particularly food water and litter containers) in the household.

2. Food - Cats prefer to eat individually in a quiet location where they will not be startled by other animals, sudden movement, or activity of an air duct or appliance that may begin operation unexpectedly. Although canned food may be preferable for cats with FIC due to the increased water content or a more natural "mouth feel", some cats may prefer dry foods. If a diet change is appropriate, offering the new diet in a separate, adjacent container rather than removing the usual food and replacing it with the new food will permit the cat to express its preference. Natural cat feeding behavior also includes predatory activities such as stalking and pouncing. These may be simulated by hiding small amounts of food around the house, or by putting dry food in a container from which the cat has to extract individual pieces or move to release the food pieces, if such interventions appeal to the cat. Also, some cats seem to have specific prey preferences. For example, some cats prefer to catch birds, while others may prefer to chase mice or bugs. Identifying a cat's "prey preference" allows one to buy or make toys that the cat will be more likely to play with.

3. Water - Cats also seem to have preferences for water that can be investigated. Water-related factors to consider include freshness, taste, movement (water fountains, dripping faucets or aquarium pump-bubbled air into a bowl), and shape of container (some cats seem to resent having their vibrissae touch the sides of the container when drinking). As with foods, changes in water-related factors should be offered in such a way that permits the cat to express its preferences. Additionally, food and water bowls should be cleaned regularly unless individual preference suggests otherwise.

4. Litter boxes - Litter boxes should be provided in different locations throughout the house to the extent possible, particularly in multiple cat households. Placing litter boxes in quiet, convenient locations that provide an escape route if necessary for the cat could help improve conditions for normal elimination behaviors. If different litters are offered, it may be preferable to test the cat's preferences by providing them in separate boxes, since individual preferences for litter type have been documented. For cats with a history of urinary problems, unscented clumping litter should be considered. Litter boxes should be cleaned regularly and replaced; some cats seem quite sensitive to dirty litter boxes. Litter box size and whether or not it is open or covered also may be important to some cats.

5. Space - Cats interact with both the physical structures and other animals, including humans, in their environment. The physical environment should include opportunities for scratching (both horizontal and vertical may be necessary), climbing, hiding and resting. Cats seem to prefer to monitor their surroundings from elevated vantage points, so climbing frames, hammocks, platforms, raised walkways, shelves or window seats may appeal to them. Playing a radio to habituate cats to sudden changes in sound and human voices also has been recommended and videotapes to provide visual stimulation are available.

6. Play - Some cats seem to prefer to be petted and groomed, whereas others may prefer play interactions with owners. Cats also can be easily trained to perform behaviors ("tricks"); owners just need to understand that cats respond much better to praise than to force, and seem to be more amenable to learning if the behavior is shaped before feeding. Cats also may enjoy playing with toys, particularly those that are small, move, and that mimic prey characteristics. Many cats also prefer novelty, so a variety of toys should be provided, and rotated or replaced regularly to sustain their interest.

7. Conflict management - When cats' perception of safety becomes threatened, they appear to respond in an attempt to restore their "perception of control". During such responses, some cats become aggressive, some become withdrawn, and some become ill. In our experience, intercat conflict commonly is present when multiple cats are housed indoors together and health problems are present. Signs of conflict between cats can be open or silent. Cats in open conflict may stalk each other, hiss, and turn sideways with legs straight and hair standing on end up to make themselves look larger. In contrast, signs of silent conflict can be easily missed; threatened cats may avoid other cats, decrease their activity, or both. They often spend increasingly large amounts of time away from the family, stay in areas other cats do not use, or attempt to interact with family members only when the assertive cat is elsewhere. Signs can result from two types of conflict; offensive and defensive. In offensive conflict, the assertive cat moves closer to the other cats, to control the interaction. In defensive conflict situations, threatened cats attempt to increase the distance between itself and the thing it perceives as a threat. Although cats engaged in either type of conflict may spray or eliminate outside the litter box, we find that threatened cats are more likely to develop elimination problems.

8. The most common cause of conflict between indoor-housed cats that we have been able to identify is competition for resources; space, food, water, litter boxes, perches, sunny areas, safe places where the cat can watch its environment, or attention from people. There may be no obvious limitation to access to these resources for conflict to develop; the cat's perceptions of how much control it wants over the environment or its housemates' behaviors determines the situation.

9. Open conflict is most likely to occur when a new cat is introduced into the house, and when cats that have known each other since kittenhood reach social maturity. Conflict occurring when a new cat is introduced is easy to understand, and good directions are available from many sources for introducing the new cat to the current residents. Clients may be puzzled by conflict that starts when one of their cats becomes socially mature, or when a socially mature cat perceives that one of its housemates is becoming socially mature. Cats become socially mature between 2 and 5 years of age, and start to take some control of the social groups and their activities. This may lead to open conflict between males, between females, or between males and females. The cats involved in the conflict may never be "best friends", but they usually can live together without showing signs of conflict or conflict-related disease. In severe cases, a behaviorist may be consulted for assistance in desensitizing and counter conditioning of cats in conflict so they can share the same spaces more comfortably if this is desired.

10. Treatment for conflict between cats involves providing a separate set of resources for each cat, preferably in locations where the cats can use them without being seen by other cats. This lets the cats avoid each other if they choose to without being deprived of an essential resource. Cats may require and use more space than the average house or apartment affords them. The addition of elevated spaces such as shelves, "kitty condos", cardboard boxes, beds, or crates may provide enough space to reduce conflict to a tolerable level. In severe situations, some cats may benefit from behavior-modifying medications. In our experience, however, medication can help only after environmental enrichment has occurred, it can not replace it. Conflict also can be reduced by neutering all of the cats, and by keeping all nails trimmed as short as practicable. Whenever the cats involved in the conflict can not be directly supervised, they may need to be separated. This may mean that some of the cats in the household can stay together, but that the threatened cat is provided a refuge from the other cats. This room should contain all necessary resources for the cat staying in it.

11. Conflict with other animals, dogs, children, or adults is relatively straightforward. In addition to being solitary hunters of small prey, cats are small prey themselves for other carnivores, including dogs. Regardless of how sure the client is that their dog will not hurt the cat, to the cat the dog represents a predator. If the cat does not assert dominance over the dog, as often happens, it must be provided ways to escape at any time. For humans, it usually suffices to explain that cats may not understand rough treatment as play, but as a predatory threat. Most cats in urban areas in the United States are housed indoors and neutered, so conflict with outside cats can occur when a new cat enters the area around the house the affected cat lives in. To cats, windows are no protection from a threatening cat outside. If outside cats are the source of the problem, a variety of strategies to make ones garden less desirable to them are available.

12. Because of the dearth of controlled trials, it currently is not possible to prioritize the importance of any of these suggestions, or to predict which would be most appropriate in any particular situation. Appropriately designed epidemiological studies might be able to identify particularly important factors, after which intervention trials could be conducted to determine their efficacy in circumstances where owners successfully implemented the suggested changes.

1. Pet History

13. Pheromones - A novel aspect of environmental enrichment that recently has become available is application of pheromones to the living space. Pheromones are chemical substances that seem to transmit highly specific information between animals of the same species. Although the exact mechanism of action is unknown at this time, pheromones appear to effect changes in the function of both the limbic system and the hypothalamus to alter the emotional status of the animals. Feliway® a synthetic analogue of naturally occurring feline facial pheromone, was developed to decrease anxiety-related behaviors of cats. Although not specifically tested in cats with FIC, treatment with this pheromone has been reported to reduce the amount of anxiety experienced by cats in unfamiliar circumstances, a response that may be helpful to these patients and their owners. Decreased spraying in multi-cat households, decreased marking, and a significant decrease in scratching behavior also has been reported subsequent to its use. Although, Feliway is not a panacea for unwanted cat behaviors or FIC, we have used it successfully in combination with environmental enrichment, and/or drug therapies.

2. Health History

Follow-Up

One of the critical keys to any successful therapy program is to follow the progress of the patient. We tell clients what our follow-up schedule is, and ask them to agree to a preferred method and time to be contacted. Our first contact with the client occurs within a week after initial recommendations are made, followed by repeat "check-ins" at 3-6 weeks, 3 months, 6 months, and 1 year. This allows us to monitor the patient's progress, to make adjustments as needed, and to continue to support and motivate the client. It also helps to determine when the owner is becoming frustrated or is having problems with the plan so that encouragement or suggestions to help keep them on the plan can be offered.

3. Environmental History

Conclusions

Many indoor housed cats appear to survive perfectly well by accommodating to less than perfect surroundings. The neuro-endocrine-immune abnormalities in the cats we treat, however, do not seem to permit the adaptive capacity that healthy cats enjoy, so these cats may be considered a separate population with greater needs. Moreover, veterinarians are concerned more with optimizing the environments of indoor cats than with identifying minimum requirements for indoor survival. My current approach is to let the client choose the most appropriate intervention for their particular situation, and to let technicians do the enrichment implementation and follow-up (under veterinary supervision as appropriate). Finally, the question of the relative merits of indoor housing to promote the welfare of cats (and the different opinions on what constitutes animal welfare in general) is beyond the present scope, and is a subject of controversy among experts. I hope to encourage extension of the welfare efforts of individuals working in zoos, who have recognized the effects of the quality of housing on the health on animals in their care and worked to enrich the environments of these animals, to all "captive animals" in our care. I believe that FIC and a variety of related disorders may be better prevented than treated, and that we have a huge opportunity to encourage this husbandry approach in veterinary clinical practice. Further information about environmental enrichment for indoor housed cats is available at: http://indoorpet.osu.edu/

4. Household Resource Checklist

References - available on request